Elucidation of Sulforaphane‐Mediated Effects on the Cellular Human Metabolome Using Metabolic Profiling

Bieß, N; Behrens, M; Humpf, H-U; Gerdemann, A

Abstract

Sulforaphane (SFN) is an isothiocyanate derived from glucoraphanin, which occurs in broccoli. Several human health-promoting effects are attributed to the consumption of cruciferous vegetables or food supplements containing SFN. Its described cancer-preventive, chemoprotective, and antioxidant properties made SFN an increasingly important research topic. The antioxidant properties have previously been connected to stimulation of the Nuclear factor erythroid-2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) signaling pathway. However, the global effects of SFN on the primary metabolic pathways have yet to be fully unraveled. Therefore metabolic profiling was used to elucidate the effects of SFN on the cellular metabolome. For this purpose, human hepatoblastoma cells (HepG2) were incubated with SFN and the changes of primary metabolite levels were determined by targeted hydrophilic interaction liquid chromatography tandem mass spectrometry (HILIC-MS/MS) analysis. Metabolic profiling revealed that SFN affects the tricarboxylic acid cycle, the urea cycle and their related amino acids. Furthermore, effects on glycolysis, pentose phosphate pathway and glutathione (GSH) levels were observed. This profound impact on nearly all primary metabolic pathways indicates a high bioactive potential of this natural compound. Especially elevated GSH levels underline the commonly described antioxidant potential of SFN.